Application Archives - Center for Innovative Technology /cit Integrated ‘omics’ capabilities utilizing state-of-the-art multi-dimensional mass spectrometry and automated high content microscopy Tue, 14 Jan 2020 21:52:20 +0000 en-US hourly 1 https://wordpress.org/?v=5.8 https://cdn.vanderbilt.edu/vu-wp0/wp-content/uploads/sites/166/2019/02/27124736/WholeGear_Transparent-32x32.png Application Archives - Center for Innovative Technology /cit 32 32 Small Molecule Omics and Cancer Biology /cit/small-molecule-omics-cancer-biology/ Tue, 14 Jan 2020 15:07:10 +0000 /cit/?p=1474 The post Small Molecule Omics and Cancer Biology appeared first on Center for Innovative Technology.

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Small Molecule Omics and Cancer Biology


“Oncometabolites” initiate or sustain cancer tumor growth and metastasis. The term oncometabolite was first used for 2- hydroxyglutarate, as it was found to activate hypoxiainduced, oncogenic pathways and affect DNA methylation, specifically in gliomas and acute myeloid leukemia.1 Understanding metabolic factors that enable cancer cell proliferation and finding reprogrammed metabolic pathways has led to several other oncometabolic targets (or metabolites) to be discovered.2-4 Of the metabolites involved in cancer biology, lipids have not only been shown to be involved in intracellular signaling of cancer cells, but de novo lipid synthesis has been found to be a key metabolic activity in cancer cell growth and survival and targeting lipid metabolic pathways has been shown to affect chemosensitivity.3,5 Previous data has also shown that branched-chain amino acid (BCAA) can serve as metabolic substrates in several types of cancer.6



The CIT has developed a conformational lipid atlas containing highly-accurate structural measurements in support of high-confidence lipidomic annotations. This lipid atlas is available in the CIT to help us and our collaborators better understand the role of lipids in cancer. Please contact us if you are interested in performing analyses to determine which lipids may be contributing to or reprogramming cancer cell proliferation in your specific biological system.

In addition, the CIT has also developed a qualitative amino acids MS-based assay that can be applied to diverse biological sample types (e.g. plasma, serum, urine, cells or tissue) without the need for tagging. These analyses are performed with high precision (≤ 5 ppm) and low variability (≤ 10% RSD).



References:

  1. Wishart DS, Emerging applications of metabolomics in drug discovery and precision medicine, Nat Rev Drug Discov 2016, 15, 473-484.
  2. Luengo A et al., Targeting Metabolism for Cancer Therapy, Cell Chem Biol 2017, 24, 1161-1180.
  3. Röhrig F et al., The multifaceted roles of fatty acid synthesis in cancer, Nat Rev Cancer 2016, 16, 732-749.
  4. Adams JL et al., Big opportunities for small molecules in immuno-oncology, Nat Rev Drug Discov 2015, 14, 603-622.
  5. Beloribi-Djefaflia S, Vasseur S, Guillaumond F, Lipid metabolic reprogramming in cancer cells, Oncogenesis 2016, 5, e189.
  6. Mayers JR, et al., Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers, Science 2016, 353, 1161-1165.

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Collision Cross Section Data
Metabolite Annotations
Katrina Leaptrot, Post Doc in the McLean Lab
Large Metabolomics Studies
High-Throughput Multi-Omic Analyses
qualitative amino acid panel

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The Human Microbiome’s Metabolome /cit/the-human-microbiomes-metabolome/ Wed, 31 Jul 2019 08:58:20 +0000 /cit/?p=1398 The post The Human Microbiome’s Metabolome appeared first on Center for Innovative Technology.

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The CIT is Excited to be a Part of the ý Microbiome Initiative


Microbiota are diverse and changing dynamically. The human microbiome plays an important role in our health and its composition and functionality is influenced by a variety of factors such as nutrition, environmental and pharmaceutical exposures, stress, and lifestyle. Several specific interactions between the microbiome’s and host’s metabolomes have been observed and described as co-metabolism via global, untargeted mass spectrometry analysis.1-4

Several microbiome-host interactions currently under investigation are shown in Figure 2 below. Examples for such interactions include bidirectional communication between liver and gut microbiota, in which liver metabolites influence gut microbiota composition thereby affecting intestinal barrier integrity. At the same time, gut microbiota also affect regulation of bile acid synthesis, glucose and lipid metabolism in the liver.5Microbiome metabolites have also been shown to affect depression, anxiety, and cognition in bidirectional communication across the gut-brain axis via neurocrine, endocrine, and inflammatory signals.6

The CIT is proud to be a member of the newly established Vanderbilt Microbiome Initiative and looks forward to support collaborators in further investigating the interesting relationship and interactions between host and microbiome metabolomes. We offer full-service, streamlined workflows, cutting edge untargeted and targeted molecular omics (incl. metabolomics, lipidomics, amino acids) resources for data acquisition and analysis, and a collaborative approach that enables our collaborators to focus on what matters most to them.

For a consultation, funding application support, or custom method development, please contact us today.

To read more about the ý Microbiome Initiative, please visit their website:

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Advancing Lipidomics /cit/lipidomics/ Wed, 17 Apr 2019 12:16:10 +0000 /cit/?p=1349 The post Advancing Lipidomics appeared first on Center for Innovative Technology.

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High Confidence Lipidomics via a Lipid Structure Atlas Enables the CIT to Predict Dysregulation

Lipids play an important role in health and disease, such as de novo lipid synthesis in cancer cell growth and survival or dysregulation of lipid metabolism in neurodegenerative diseases. Yet lipidomics research, the study of lipid species, pathways and their interactions with other metabolites inside an organism, is considered an emerging discipline. To advance the field, high-precision ion mobility-mass spectrometry resources in the CIT were utilized to develop a conformational database for lipids.

The atlas includes collision cross section information for numerous lipid classes, including: sphingomyelin, cerebroside, ceramide, phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, and phosphatidic acid. The figure below outlines the important correlations that were discovered for glycerophospholipids (PS) and sphingolipids (GlcCer). This lipid atlas is available in the CIT to help collaborators better understand the role of lipids in their specific disease.

Katrina Leaptrot, Post Doc in the McLean Lab

Read the publication:
Read the ý News article:
Read the ý Institute of Chemical Biology’s summary article: /vicb/discovery_featured3.html



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Liquid Handling Platform Added for Large Metabolomics Studies /cit/large-metabolomics-studies/ Thu, 28 Feb 2019 13:14:58 +0000 /cit/?p=1069 The post Liquid Handling Platform Added for Large Metabolomics Studies appeared first on Center for Innovative Technology.

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Liquid Handling Platform Will Enable Increased Throughput for up to 3,000 Samples/Setup


Manual sample handling is labor-intensive and can contributes to the technical variability of analytical results. In comparison, automated liquid sample handling provides increased overall sample throughput, enabling larger sample sets to be analyzed more efficiently and with minimal technical variation.

In collaboration with Prof. Renã Robinson’s lab, the Center for Innovative Technology (CIT) has acquired a Beckman Coulter Biomek i-7 Automated Liquid Handling Workstation that will be available as a resource for molecular omics studies at the CIT. Center staff are completing all necessary hands-on training in order to successfully integrate this new resource into our workflows.

The workstation will enable the CIT to serve large-scale projects with several hundred or thousand samples in an efficient and highly reproducible manner.



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Qualitative Amino Acid Panel /cit/qualitative-amino-acid-panels/ Mon, 21 Jan 2019 13:12:39 +0000 /cit/?p=998 The post Qualitative Amino Acid Panel appeared first on Center for Innovative Technology.

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New Service:

Qualitative Amino Acid Panel


Amino acids, often referred to as the building blocks of proteins, are compounds that play many critical roles in the body. They are needed for vital processes like the building of proteins and biosynthesis of hormones and neurotransmitters. In addition, they can be predictors of outcome in heart failure, hepatobiliary and some cancers, as well as markers for prediabetes (glycine), type 2 diabetes (valine, leucine, isoleucine, phenylalanine and tyrosine) or kidney function (tryptophan-kynurenine ratio).

The CIT has developed a 20 amino acids MS-based assay that can be applied to diverse biological sample types (e.g. plasma, serum, urine, cells or tissue). These analyses are performed with high precision (≤ 5 ppm) and low variability (≤ 10% RSD).

See image below for an extracted ion chromatogram of individual amino acids.


qualitative amino acid panel


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Discovery-Based Metabolomics Reveals MBLAC1 Functionality /cit/discovery-based-metabolomics/ Tue, 08 Jan 2019 15:13:04 +0000 /cit/?p=991 The post Discovery-Based Metabolomics Reveals MBLAC1 Functionality appeared first on Center for Innovative Technology.

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Discovery-Based Metabolomics Lifts the Curtain on MBLAC1 Gene’s Functional Roles


A research project lead by Professor Blakely (Florida Atlantic University) in collaboration with the Center for Innovative Technology (CIT) at Vanderbilt has been investigating the physiological role of the MBLAC1 gene via global, untargeted mass spectrometry analysis. In the serum metabolome the team was able to discover unique differences in primary bile acid biosynthesis and linoleate metabolism between MBLAC1 knock-out and age-matched wild-type mice. Future targeted metabolomics studies are expected to reveal the MBLAC1 substrate and its related neuroprotective effects.

The full, peer-reviewed publication can be found .



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